My long-term goal is to explore the link between obesity, insulin resistance, and hypertension in humans. Obesity is associated with increased levels of sympathetic activity, which may be a risk factor in the development of hypertension. Obesity is also associated with insulin resistance. Since obesity does not always result in hypertension, and increased levels of sympathetic activity are not always associated with hypertension, this raises the possibility that increased sympatetic activity and insulin resistance interact to promote hypertension in obese humans. Further, insulin is a potent vasodilator that can blunt sympathetic vasoconstriction in normal subjects. Thus, the development of insulin resistance in conjunction with increased sympathetic activity might promote the development of hypertension in the obese individual. In this context, it is possible that the relation between sympathetic nerve activity and vascular resistance is altered by the development of insulin resistance in obese individuals to favor vaso constriction. Therefore, we speculate that sympathetic vasoconstriction will be greater and vascular resistance will be higher in obese individuals because insulin resistance blunts the vasodilatory actions of insulin, permitting unopposed sympathetic vasoconstriction to occur. If so, this might be a key factor which links obesity, augmented sympathetic activity, and insulin resistance in the development of hypertension in obese humans. In this proposal we will tes the idea that insulin resistance exacerbates the hypersive effects of increased sympathetic nerve activity in viscerally obese indviduals.